SUMMARYCryptosporidiumis a protozoan parasite of medical and veterinary importance that causes gastroenteritis in a variety of vertebrate hosts. Several studies have reported different degrees of pathogenicity and virulence amongCryptosporidiumspecies and isolates of the same species as well as evidence of variation in host susceptibility to infection. The identification and validation ofCryptosporidiumvirulence factors have been hindered by the renowned difficulties pertaining to thein vitroculture and genetic manipulation of this parasite. Nevertheless, substantial progress has been made in identifying putative virulence factors forCryptosporidium. This progress has been accelerated since the publication of theCryptosporidium parvumandC. hominisgenomes, with the characterization of over 25 putative virulence factors identified by using a variety of immunological and molecular techniques and which are proposed to be involved in aspects of host-pathogen interactions from adhesion and locomotion to invasion and proliferation. Progress has also been made in the contribution of host factors that are associated with variations in both the severity and risk of infection. Here we provide a review comprised of the current state of knowledge onCryptosporidiuminfectivity, pathogenesis, and transmissibility in light of our contemporary understanding of microbial virulence.